The present invention relates to prodrug derivatives of dabigatran, their use for the treatment and/or prophylaxis of diseases, in particular thrombotic diseases, stroke, cardiac infarction and/or atrial fibrillation and cardiac arrhythmia, as well as oncological diseases of any pathogenesis.
Within the last few years, dabigatran etexilate (Pradaxa®) has been established in thrombosis prevention after hip and knee replacement surgeries. In addition, this active agent was approved for further fields of indication (atrial fibrillation, stroke prevention and secondary prevention after heart attack, acute coronary syndrome). In the long run, further promising fields of indication are also conceivable, in particular in the cardiovascular field, as well for cancer therapy. Despite its successful market launch, dabigatran etexilate also has unfavorable substance properties which can limit its wide use.
Thus, dabigatran etexilate, i.e., a prodrug of the actual active substance dabigatran, for example, is of very poor solubility, which results in some disadvantages both in the usage as well as preparation of the medicinal product. To improve the solubility of the compound, the medicinal substance is applied onto pellets containing tartaric acid which is very cost-intensive due to a considerable technical expenditure for preparing this galenic form. Moreover, the bioavailability is adversely affected by the poor solubility of the compound so that the medication consists of two capsules, which in turn negatively influences patient compliance.